Saturday 15 December 2018

Could the link between gut bacteria and the brain help treat disorders like anxiety and depression?

Neuroscientists are only starting to study the links between gut bacteria and the brain, writes Jamie Ball, and it may change how we treat disorders like anxiety and depression

Gut bacteria
Gut bacteria

Jamie Ball

For those of you who assumed the reasoning behind "gut instinct" or "going with your gut" or "feeling gutted" or "butterflies in your tummy" to be groundless old wives' tales, science is asking you to think again.

Mounting evidence over the last decade suggests that gut microbes help shape normal neural development and brain biochemistry. And while the science continues to unfold the mysteries of how and why the microbiota-brain axis so deeply influences our mood and behaviour, it is hoped research will reveal innovative, diet-based treatments not just for depression and anxiety, but for the likes of Parkinson's, Alzheimer's, autism and schizophrenia too.

The intestine and the brain are closely connected through the bidirectional communication of the brain-gut axis, which comprises of interactions with intestinal microbiota, or gut bacteria. These release immune-activating molecules that have the potential to play a crucial part in brain regulation, impacting upon our mood, thoughts and behaviour.

"It will remain that the heart is our emotional centre for love and romance," says Professor Jane Foster of the Department of Psychiatry and Behavioural Neurosciences at McMaster University in Ontario, Canada.

"However, there is a place for gut feelings in understanding the biological pathways that influence mood and mental health, which are, in fact, quite distinct. Neuroscientists and others are only just starting to study the ways that microbiota influence the brain."

Foster says the latest research demonstrates a central role for gut microbiota in our normal healthy metabolism, as studies show that disruption or alterations in the profile of gut microbiota can increase the risk of metabolic disorders, such as obesity and diabetes.

"Recent work studying communication between the brain and the gut have also identified a functional link between gut microbiota and brain function, with particular attention to depression and anxiety," adds Foster.

Enter probiotics. Defined simply as "microorganisms that are believed to provide health benefits when consumed", probiotics have only entered the general consumer's radar over the last quarter century, most typically in association with certain yoghurts. But the research behind probiotics dates back over a century. In 1907, Nobel laureate, Élie Metchnikoff, had originally suggested that intestinal microbes' dependence on diet allows us to replace harmful microbes with useful ones.

However, the numerous beneficial claims made about using commercial probiotics are not always backed up by scientific evidence. And while most conclusive scientific research on this topic to date has been carried out on rodents, two separate studies in recent years provide greater hope.

A 2013 study by the Oppenheimer Family Centre for Neurobiology of Stress at the Department of Medicine in UCLA, California, established that the consumption of a fermented milk product with a yoghurt-based probiotic for four weeks by healthy women affected activity of brain regions that "control central processing of emotion and sensation".

Furthermore, a 2015 triple-blind assessment by scientists at the Netherlands' Leiden University's Institute for Psychological Research, used a multi-species probiotic food supplement on 20 healthy adults over four weeks. The results provided the "first evidence that the intake of probiotics may help reduce negative thoughts associated with sad mood. Probiotics supplementation warrants further research, as a potential preventive strategy for depression".

Which is where probiotics enters the field of psychobiotics; a live microorganism, which when administered in adequate amounts, confers a health benefit in patients suffering from psychiatric illness.

"While much of the early work suggesting the microbiota influence brain function and behaviour came from animal studies," says Foster, "evidence is accumulating from studies in healthy individuals and in clinical populations that probiotics reduce depressive and anxiety-related symptoms, but also reduce the body's physiological response to stress, where individuals receiving probiotics have lower levels of circulating stress hormones."

It appears there is massive microbiome potential this century for the prevention or treatment of certain brain-related illnesses. One case in point is Parkinson's disease: the gut microbes of those suffering from Parkinson's have been found to be radically different to non-sufferers. However, whether such degenerative diseases can be effectively treated by altering the gut microbe composition remains to be seen. In addition, it is still too early to tell whether psychobiotics could, in time, come to replace conventional anti-depressants, but it's arguably neuroscience's key challenge for the next decade.

"Our bacteria development early in life is needed for early brain development, and perhaps an imbalance might be a predisposing factor for a number of brain disorders," says Professor John Cryan in his 2015 TEDMED talk. A neuropharmacologist and microbiome expert from University College Cork, Cryan has published over 190 peer-reviewed articles and book chapters.

"In the 20th century we focused on killing microbes with antibiotics - that was the major focus. Over the last number of years we have really appreciated that microbes have so much benefit and that their power can be harnessed in both health and disease.

"So perhaps the secret to our own happiness may not lie in the self-help section of the local bookstore, but maybe within your microbiome, and that your state of mind might be dependent on your state of gut."

Good gut, bad gut

Microbes can be found in many parts of our bodies, such as our skin and lungs, where they play an important role in host-environment interactions. But we have way more bacteria in our intestines than we do cells in our body, and therefore gut microbes capture the most attention.

These are critical to the healthy development of our immune system and our brains, as "good" gut bacteria helps us digest complex polysaccharides in our diet, which play a critical role in the normal development of the immune system.

It's also been discovered that the industrialisation of developed nations over the last couple of centuries has wiped out some of the diversity and richness of microbes that our descendants would have shared, as emulsifiers and sweeteners, for example, as well as processed food, have done little to help our microbe composition.

However, a tenable link between the consumption of such foods and the onset of mental illnesses, or brain-related degenerative diseases, has yet to be established, but we are likely to know a lot more over the next five to 10 years about how water-tight and verifiable any such link may be.

According to Professor Jane Foster of McMaster University in Ontario, the composition of our microbiota is influenced by both our own genetics and by the environment (diet, stress, exercise, antibiotics and other medications) and by other important factors (age and gender).

"We are not able to change our own genetics but we may be able to influence it through other choices, such as how gene-environment interactions influence our microbiota and our health.

"From my perspective the most important threat to the gut microbiota, with respect to mental health, is early life environment including diet, stress and medications. These influence microbiota but also influence brain wiring and may influence risk of disease later in life."

According to Foster, antibiotics definitely reduce the diversity and composition of the microbiota, but she is cautious about overstating the perceived damage.

"Following a short course of antibiotics, our gut microbiota return to normal. It is likely that chronic or repeated exposure to antibiotics would be associated with more permanent damage to the system. In fact, in some situations, a short course of antibiotics has a mood-elevating effect. This might relate to the reduced inflammation or the anti-inflammatory effects of this type of medication."

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